13C-methacetin breath test for evaluating of children's liver disorder / 中华实用儿科临床杂志

Objective To explore the clinical value of 13C-methacetin breath test for the assessment of liver disorder and to analyze its predictive value to the severity of liver function injury in children.Methods Eighteen healthy children served as healthy control group,and 40 patients with different etiology and severity served as experimental group,and then the latter were divided into 2 subgroups,28 patients in Child-Pugh classification A,and 12 cases in below B(11 cases in B and 1 case in C).An oral dose of 2 mg/kg tracer 13C-methacetin was administered to each subject for the 13 C-methacetin breath test.At the same time,serum liver function markers including serum transaminase,bilirubin,albumin and prothrombin time were measured.The acquired data were analyzed by SPSS 17.0 software.Results (1) Metabolisation velocity (MV) max30 and cumulated dose (CUM) 120 in experimental group (46.64 ± 27.93,59.29 ± 30.73) were much lower than those of the healthy control group(73.56 ± 26.03,102.97 ± 41.80) (t =2.450,3.165,all P ＜0.05);(2) MVmax30 and CUM120 were closely correlated with the liver function markers of albumin,total bilirubin,direct bilirubin,prothrombin time (P ＜ 0.05);(3) MVmax30 and CUM120 could predict liver diseases in children,especially the CUM120.With CUM120 =85.80 as a cut-off value to predict liver diseases,the Youden index was 0.578 at its maximum,and the sensitivity and specificity were 77.8％ and 80.0％;(4) Compared with the Child-Pugh classification A,the CUM120 in Child-Pugh classification B and lower B was significantly lower(P ＜ 0.001);(5) CUM120 could predict the severity of liver diseases.With CUM120 =56.15 as a cut off value to predict the severity of liver diseases,the Youden index was 0.857 at its maximum,and the sensitivity and specificity were 85.7％ and 100.0％.Conclusion 13C-methacetin breath test index of CUM120 could predict liver diseases in children and the severity of liver function.

Prueba de aliento con 13C-metacetina en el diagnóstico y manejo de las enfermedades hepáticas / Breath tests with 13C-methacetin in the diagnosis and management of liver disease

Resumen: una prueba diagnóstica, incluidas las del laboratorio clínico, las de patología y las de radiología en sus múltiples aplicaciones, es de utilidad clínica cuando su desempeño analítico alcanza indicadores de precisión y exactitud ideales, es decir, lo más cercano al 100%, cuando se utiliza en el diagnóstico, clasificacióny manejo de un grupo de enfermedades para las cuales se ha diseñado. En el caso de las enfermedadeshepáticas, ninguna de estas pruebas, hasta el momento disponibles, logra este objetivo e incluso están lejos de alcanzarlo, aun cuando son críticas en el diagnóstico y manejo de estas enfermedades. Con el descubrimiento de que el estómago podía ser colonizado con una bacteria, hoy denominada Helicobacterpylori, y el desarrollo posterior de la prueba de aliento con urea marcada con carbono 13 (13C-urea), múltiples pruebas de aliento han sido desarrolladas con sustratos marcados con 13C, siendo la prueba de aliento 13C-metacetina la más representativa para determinar la función hepática por esta metodología. En este módulo se presenta la prueba de aliento con 13C-metacetina como una nueva alternativa, no invasiva, para el estudio de la función hepática en el diagnóstico y seguimiento de las enfermedades del hígado. Además, se presentan los fundamentos de la prueba, los métodos para realizala, la interpretatición de los resultados, las limitaciones y las indicaciones de la misma.

Abstract: a diagnostic test, including those of clinical laboratory, pathology and radiology, in its many applications, it is clinically useful when their analytical performance achieves ideal accuracy indicators,namely as close to 100%, when it used in diagnosis, classification and management of a group of diseases for which it is designed. In the case of liver disease, none of these tests so far available, achieves this goal and are far from reaching it, even though they are critical to diagnosis and managementof these diseases. With the discovery that the stomach could be colonized with bacteria, now called Helicobacter pylori, and the subsequent development of the carbon 13-labeled urea (13C-urea) breath test, different breath tests have been developed with 13C labeled substrates, being the 13C-methacetin breath test the most representative to determine liver function by this methodology. In this module is presents the 13C-methacetin breath test as a new alternative, non-invasive, for the study of liver function in the diagnosis and monitoring of liver diseases. In addition, are describing the basics of test methods to perform it, the interpretation of results, limitations, and indications of it.

Role of 13C methacetin breath test for non invasive staging of liver fibrosis in patients with chronic hepatitis C.

Background & objectives: The development and evaluation of non invasive tests to assess liver fibrosis have been an active field of research. The present study was carried out to evaluate the role of 13C-methacetin breath test (13C- MBT) as a non invasive tool for liver fibrosis staging in patients with chronic hepatitis C (CHC). Methods: 13C-Methacetin breath test was performed in 115 patients with CHC histologically proven and in 55 healthy controls. All patients and controls underwent routine liver function tests. The CHC patients underwent histological assesment of liver by percutaneous liver biopsy. The correlation between the 13C-methacetin breath test and liver biopsy was tested using Kendall’s rank correlation coefficients. The overall validity was expressed as area under receiver operating characteristic curve (AUROC) with 95%CI. Results: Delta over baseline values (DOB) of CHC patients at 20 min were significantly reduced compared with control (16. 2 vs. 21. 06%, p<0.001). There were also significant differences between CHC patients and controls as regard the metabolization speed (dose /h at 20 min (17.80 vs 28.6, p<0.001) and metabolization capacity (cumulative recovery after 60 min (13.8 vs 20.4 p<0.001). The best 13C-MBT parameter correlated with fibrosis was DOB at 20 min (r= - 0.596). The optimal cut-off for the diagnosis of advanced fibrosis (F≥3) was 15.2 per cent, with AUROC= 0.902, 95%CI: (0.851-0.938), a sensitivity of 82 per cent and a specificity of 80 per cent. DOB at 20 min predicted even better cirrhosis: AUROC = 0.932 95 per cent CI = 0.901-0.953, a sensitivity of 96 per cent and a specificity of 92 per cent. Interpretation & conclusions: Based on our findings the 13C – methacetin breath test appears to be a promising tool to identify CHC patients with advanced fibrosis and to replace liver biopsy. fFurther studies need to be done to assess its potential to be used in regular clinical practice.

The study of reserved liver function after TACE in hepatic carcinoma by 13C-methacetin breath test / 肿瘤研究与临床

Objective To investigate the changes of hepatic function before and after transcatheter arterial chemoembolization (TACE) in primary liver cancer patients with different quantifications and classifications using 13C-methacetin breath test (13C-MBT), and to provide risk predicts for TACE. Methods 28 cases of primary liver cancer patients and 10 cases of metastatic liver cancer patients were selected.General examination items of liver function and 13C-MBT detection were performed on all cases. Primary liver cancer was divided into 4 groups according to the results of 13C-MBT (group 1 was normal or pathological liver damage; group 2 was grade A; Group 3 was grade B; group 4 was grade C). 13C-MBT detection was carried out in week 1 and 4 after TACE. Results The three parameters of 13C-MBT is 13CO2 maximum excretion rate before 40 min/27 (MVmax40), 13CO2 cumulative excretion of 40 min/12 (CUM40), and than of 120 min/28(CUM120). Compared with the parameters [(0.628±0.191)%, (0.628±0.289)%, (0.577±0.286)%] before TACE in hepatic metastasis, there were no statistic effect between week 1 [(0.600±0.187)%, (0.559±0.189)%, 0.587±0.181)%] and week 4 [(0.700±0.230)%, (0.734±0.229)%, (0.724±0.252)%] after TACE. Conclusion The lower classification of 13C-MBT, the more impairment to liver function after TACE. This could provide an important diagnostic basis for TACE.

Evaluation of mouse acute liver damage by breath test with domestically synthesized ~(13)C-methacetin / 上海交通大学学报（医学版）

Objective To establish a convenient ~(13)C-breath test system in live mice,and investigate the value of ~(13)C-methacetin breath test(~(13)C-MBT) in the diagnosis of acute liver damage of mice with domestically synthesized ~(13)C-methacetin. Methods Domestically synthesized ~(13)C.methacetin was prepared from aeamol by methylation. Abdominal injection of CCl_4 was adopted to duplicate acute liver damage of mice,then the mice were housed under normal laboratory condition for a whole month to gain recovery,which were indentified by hepatic pathological examinations and biochemical teats of liver function.After fasting, the mice were orally administered ~(13)C-methacetin,and the expired air was collected at various time points. Infrared spectrometer was employed, and delm over baseline(DOB) curves of ~(13)C-exhalation were drawn. Results Six to eight min after administration of ~(13)C-methacetin,the rate of ~(13)C-exhalation peaked in control group(51.9±2.04), and decreased thereafter. Sixteen min after administration of ~(13)C-methacetin,the rate of ~(13)JC-exhalation peaked in model group(26.37±5.74), and decreased thereafter.There were significant differences between these two groups(P<0.05).There was no significant difference in peak value and time to reach the peak on DOB curves of ~(13)C-methacetin breath test after the two groups of mice were housed under the same condition for a month(P>0.05).Conclution ~(13)C-MBT facilitates the collection and evaluation of ~(13)CO_2 in the expired air of live mice,and yields precise reflection of alterations of liver function in acute liver injury and functional recovery.

Evaluation the liver reservation functions of patients with severe hepatopath of nonage treated with plasma exchange by 13C-methacetin breath test / 中国综合临床

Objective To judge the effect of plasma exchange (PE) to the patients with severe hepatopath of nonage according to evaluating the change of the liver function of reserve with 13C-methacetin breath test. Methods There are two groups: the case group and the control group. Each group has 30 patients. The patients in the case group were treated by PE. All the patients received 13C-methacetin breath test at before or one week after treatment. MVmax40, CUM40 and CUM120 were present. At the same time, clinical symptoms, glutamate-pyruvate transaminase (ALT), total bilirubin (TBiL) and prethrombin active (PTA) were observed. Results MVmax40, CUM40, CUM120 and PTA were higher, ALT and TBiL were lower in the case group after treatment (t=4.679, 4.752, 5.048, 5.413, 6.208, 7.413, P=0.000,P<0.01). After a week, MVmax40, CUM40, CUM120 and PTA were higher, ALT and TBiL were lower in the case group than that in the control group (t=2.260, 2.247, 2.476, 4.017, 3.250, 3.658, P<0.05). The total effective rates in the case group and the control group were 83.3 % (25/30) and 43.3 % (13/30),which are significant different(χ2 10.335,P<0.01). Conclusion PE can im-prove the liver reservation functionin the severe hepatopath of nonage.

The value of studying liver function reserve in hepatic carcinoma by 13C-methacetin breath test / 中华内科杂志

Objective To investigate the characteristic of 13C-methacetin breath test (13C-MBT) as a tool to monitor the hepatic function of patients with hepatic carcinoma by comparing with Child-Pugh classification and general liver function. Methods Thirty-nine patients with primary liver cancer, 16 patients with hepatic metastasis and 14 healthy volunteers serving as controls were included in this study. According to Child-Pugh classification, the primary liver cancer patients were divided into A, B and C subgroups. All subjects received 13C-MBT and routine liver function tests after an overnight fast. The three major parameters of 13C-MBT i.e. maximum excretion rate before 40 min (Mwnax40), 13CO2 cumulative excretion of 40 min(CUM40) and that of 120 min(CUM120) were recorded and the two metabolism curves (DOB curve, MV curve) were made. Results (1) In the control, hepatic metastasis and primary liver cancer groups, both the DOB curve and MV curve were similar in shape; the peak time occurred at about 20 min after administration and then the curves lowered progressively. There were significant differences between the primary liver cancer group and the other two groups, but it was not statistically different between the hepatic metastasis group and the controls. The shape was obviously distinct in the groups A, B and C of primary liver cancer. The group A had a single sharp peak curve, group B a relatively flat peak curve with a lower level for a long time after the ascending phase and group C no clear excretion peak or even a negative curve. (2) As to the three parameters of 13C-MBT, there were statistical difference between the primary liver cancer group and the other two groups(P <0. 05). Between hepatic metastasis group and controls,there was statistical difference about CUM120 (P <0. 05), but no statistical difference about Mvmax40 and CUM40. While in the three groups with primary liver cancer groups, there was statistical difference between group A and B in Mvmax40 and CUM40 ( P < 0. 05 ), but no statistical difference between group B and C. As to CUM120, there was statistical difference only between group A and C. (3) Comparing the three parameters of 13C-MBT with routine liver function tests, there was negative correlation with TBA, positive correlation with Alb, PA, ChE and no correlation with ALT, AST, TBil, γ-GT, ALP and PT. (4) There was a good consistency between 13C-MBT and Child-Pugh classification in the evaluation of liver function of patients with liver cancer ( Kappa = 0. 647, P < 0. 05 ). Conclusion The value of the three parameters of 13C-MBT is decreased with severity of the liver disease and 13C-MBT may be used to evaluate the reserved hepatic function in patients with primary liver cancer with a diagnostic value equivalent to Child-Pugh classification. The study further confirms that 13C-MBT has correlation with TBA,AIb, PA and ChE.